Mechanisms for the control of local tissue blood flow during thermal interventions: influence of temperature-dependent ATP release from human blood and endothelial cells.

NEW FINDINGS: What is the central question of this study? Skin and muscle blood flow increases with heating and decreases with cooling, but the temperature-sensitive mechanisms underlying these responses are not fully elucidated. What is the main finding and its importance? We found that local tissue hyperaemia was related to elevations in ATP release from erythrocytes. Increasing intravascular ATP augmented skin and tissue perfusion to levels equal or above thermal hyperaemia. ATP release from isolated erythrocytes was altered by heating and cooling. Our findings suggest that erythrocytes are involved in thermal regulation of blood flow via modulation of ATP release. Local tissue perfusion changes with alterations in temperature during heating and cooling, but the thermosensitivity of the vascular ATP signalling mechanisms for control of blood flow during thermal interventions remains unknown. Here, we tested the hypotheses that the release of the vasodilator mediator ATP from human erythrocytes, but not from endothelial cells or other blood constituents, is sensitive to both increases and reductions in temperature and that increasing intravascular ATP availability with ATP infusion would potentiate thermal hyperaemia in limb tissues. We first measured blood temperature, brachial artery blood flow and plasma [ATP] during passive arm heating and cooling in healthy men and found that they increased by 3.0 ± 1.2°C, 105 ± 25 ml min-1  °C-1 and twofold, respectively, (all P < 0.05) with heating, but decreased or remained unchanged with cooling. In additional men, infusion of ATP into the brachial artery increased skin and deep tissue perfusion to levels equal or above thermal hyperaemia. In isolated erythrocyte samples exposed to different temperatures, ATP release increased 1.9-fold from 33 to 39°C (P < 0.05) and declined by ∼50% at 20°C (P < 0.05), but no changes were observed in cultured human endothelial cells, plasma or serum samples. In conclusion, increases in plasma [ATP] and skin and deep tissue perfusion with limb heating are associated with elevations in ATP release from erythrocytes, but not from endothelial cells or other blood constituents. Erythrocyte ATP release is also sensitive to temperature reductions, suggesting that erythrocytes may function as thermal sensors and ATP signalling generators for control of tissue perfusion during thermal interventions.

Local temperature-sensitive mechanisms are important mediators of limb tissue hyperemia in the heat-stressed human at rest and during small muscle mass exercise.

Limb tissue and systemic blood flow increases with heat stress, but the underlying mechanisms remain poorly understood. Here, we tested the hypothesis that heat stress-induced increases in limb tissue perfusion are primarily mediated by local temperature-sensitive mechanisms. Leg and systemic temperatures and hemodynamics were measured at rest and during incremental single-legged knee extensor exercise in 15 males exposed to 1 h of either systemic passive heat-stress with simultaneous cooling of a single leg (n = 8) or isolated leg heating or cooling (n = 7). Systemic heat stress increased core, skin and heated leg blood temperatures (Tb), cardiac output, and heated leg blood flow (LBF; 0.6 ± 0.1 l/min; P < 0.05). In the cooled leg, however, LBF remained unchanged throughout (P > 0.05). Increased heated leg deep tissue blood flow was closely related to Tb (R(2) = 0.50; P < 0.01), which is partly attributed to increases in tissue V̇O2 (R(2) = 0.55; P < 0.01) accompanying elevations in total leg glucose uptake (P < 0.05). During isolated limb heating and cooling, LBFs were equivalent to those found during systemic heat stress (P > 0.05), despite unchanged systemic temperatures and hemodynamics. During incremental exercise, heated LBF was consistently maintained ∼ 0.6 l/min higher than that in the cooled leg (P < 0.01), with LBF and vascular conductance in both legs showing a strong correlation with their respective local Tb (R(2) = 0.85 and 0.95, P < 0.05). We conclude that local temperature-sensitive mechanisms are important mediators in limb tissue perfusion regulation both at rest and during small-muscle mass exercise in hyperthermic humans.